Elucidation of a biosynthetic mechanism of cyclic phosphatidic acid
| Project/Area Number |
20K19732
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 脂質メディエーター / 環状ホスファチジン酸 / リゾホスファチジン酸 / グリセロホスホジエステラーゼ / リゾホスホリパーゼ / リゾリン脂質 / 生活習慣病 / 蛍光基質 |
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| Outline of Research at the Start |
環状ホスファチジン酸(cPA)は動脈硬化予防や変形性関節症病態の抑制等の多彩な生理活性を示す内因性脂質であり、生活習慣病や加齢性疾患を制御すると考えられる。しかしながら、その生合成過程・責任酵素は十分に明らかではない。本研究ではリゾホスホリパーゼD型酵素であるグリセロホスホジエステラーゼ(GDE)ファミリーがcPA生合成活性を持つという予備的結果に基づき、GDEファミリーの機能解析を行い、細胞内におけるcPAの生合成酵素であることを明らかにし、さらに生活習慣病や加齢性疾患の抑制効果を解析する。
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| Outline of Final Research Achievements |
Cyclic phosphatidic acid (cPA) is a lipid mediator that exhibits a variety of physiological activities including prevention of atherosclerosis and suppression of osteoarthritis pathology, and is regulating lifestyle- and age-related diseases. However, its biosynthetic mechanism are not fully understood. In this study, we performed functional analysis of glycerophosphodiesterase 7 (GDE7), a lysophospholipase D-type enzyme, and found that GDE7 produces cPA in endoplasmic reticulum. Furthermore, we developed of a selective fluorescence-based enzyme assay for glycerophosphodiesterase family members GDE4 and GDE7.
These findings allow high-throughput assays of GDE4 and GDE7 activities, which could lead to the development of selective inhibitors and stimulators as well as a new treatment of lifestyle- and age-related diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
cPA生合成酵素としては、血中に存在するオートタキシンが知られている。それに対し、GDE7は小胞体内で働く膜結合性酵素である。細胞内脂質メディエーターの標的は報告が少なく、本研究成果は他の脂質メディエーター研究への応用も期待できる。また、本研究で開発した活性測定系はハイスループットスクリーニングに適用可能であり、GDE7の活性調節を介した生活習慣病や加齢性疾患に対する新規治療法の開発に繋がることが期待される。
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Involvement of acid ceramidase in the degradation of bioactive N-acylethanolamines2021
Author(s)
Tsuboi Kazuhito、Tai Tatsuya、Yamashita Ryouhei、Ali Hanif、Watanabe Takashi、Uyama Toru、Okamoto Yoko、Kitakaze Keisuke、Takenouchi Yasuhiro、Go Shinji、Rahman Iffat Ara Sonia、Houchi Hitoshi、Tanaka Tamotsu、Okamoto Yasuo、Tokumura Akira、Matsuda Junko、Ueda Natsuo
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Journal Title
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Volume: 1866
Issue: 9
Pages: 158972-158972
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Identification of a chemical chaperone for mitigating protein aggregation and proteotoxicity during endoplasmic reticulum stress2021
Author(s)
Keisuke Kitakaze, Shusuke Taniuchi, Eri Kawano, Yoshimasa Hamada, Masato Miyake, Miho Oyadomari, Hirotatsu Kojima, Hidetaka Kosako, Tomoko Kuribara, Suguru Yoshida, Takamitsu Hosoya, Seiichi Oyadomari
Organizer
Experimental Biology 2021
Related Report
Int'l Joint Research
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[Presentation] Role of Acid Ceramidase in the Hydrolysis of Anti-inflammatory and Anorexic N-Acylethanolamines2021
Author(s)
Kazuhito Tsuboi, Tatsuya Tai, Ryouhei Yamashita, Hanif Ali, Takashi Watanabe, Toru Uyama, Yoko Okamoto, Keisuke Kitakaze, Yasuhiro Takenouchi, Shinji Go, Iffat Rahman, Hitoshi Houchi, Tamotsu Tanaka, Yasuo Okamoto, Akira Tokumura, Junko Matsuda, Natsuo Ueda
Organizer
Experimental Biology 2021
Related Report
Int'l Joint Research
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[Presentation] ATF4を介した転写制御は小胞体ストレスによる膵β細胞の喪失を防ぐ2021
Author(s)
北風圭介, 親泊美帆, 張君, 濱田良真, 竹之内康広, 坪井一人, 稲垣舞, 立川正憲, 藤谷与士夫, 岡本安雄, 親泊政一
Organizer
第62回日本生化学会中国・四国支部例会
Related Report
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